Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chronic Myeloproliferative Neoplasias

Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy

Leukemia volume 24, pages 1299–1301 (2010)Cite this article

Subjects

Abstract

Nilotinib is a highly selective Bcr–Abl inhibitor approved for imatinib-resistant chronic myeloid leukemia (CML). Nilotinib and dasatinib, a multi-targeted kinase inhibitor also approved for second-line therapy in CML, have different patterns of kinase selectivity, pharmacokinetics, and cell uptake and efflux properties, and thus patients may respond to one following failure of the other. An international phase II study of nilotinib was conducted in CML patients (39 chronic phase (CP), 21 accelerated phase (AP)) after failure of both imatinib and dasatinib. Median times from diagnosis of CP or AP to nilotinib therapy were 89 and 83 months, respectively. Complete hematological response and major cytogenetic response (MCyR) rates in CP were 79% and 43%, respectively. Of 17 evaluable patients with CML-AP, 5 (29%) had a confirmed hematological response and 2 (12%) a MCyR. The median time to progression has not yet been reached in CP patients. At 18 months 59% of patients were progression-free. Median overall survival for both populations has not been reached, and the estimated 18-month survival rate in CML-CP was 86% and that at 12 months for CML-AP was 80%. Nilotinib is an effective therapy in CML-CP and -AP following failure of both imatinib and dasatinib therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Giles FJ, O′Dwyer M, Swords R . Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia 2009; 23: 1698–1707.

    Article  CAS  Google Scholar 

  2. O′Hare T, Eide CA, Deininger MW . Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood 2007; 110: 2242–2249.

    Article  Google Scholar 

  3. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009; 27: 6041–6051.

    Article  CAS  Google Scholar 

  4. Hochhaus A, O′Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009; 23: 1054–1061.

    Article  CAS  Google Scholar 

  5. Quintas-Cardama A, Kantarjian H, Jones D, Nicaise C, O′Brien S, Giles F et al. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood 2007; 109: 497–499.

    Article  CAS  Google Scholar 

  6. Goldman JM . Chronic myeloid leukemia: reversing the chronic phase. J Clin Oncol 2010; 28: 363–365.

    Article  CAS  Google Scholar 

  7. Jabbour E, Hochhaus A, Cortes J, La Rosee P, Kantarjian HM . Choosing the best treatment strategy for chronic myeloid leukemia patients resistant to imatinib: weighing the efficacy and safety of individual drugs with BCR-ABL mutations and patient history. Leukemia 2010; 24: 6–12.

    Article  CAS  Google Scholar 

  8. Hiwase DK, Saunders V, Hewett D, Frede A, Zrim S, Dang P et al. Dasatinib cellular uptake and efflux in chronic myeloid leukemia cells: therapeutic implications. Clin Cancer Res 2008; 14: 3881–3888.

    Article  CAS  Google Scholar 

  9. Eadie L, Hughes TP, White DL . Nilotinib does not significantly reduce imatinib OCT-1 activity in either cell lines or primary CML cells. Leukemia 2010; 24: 855–857.

    Article  CAS  Google Scholar 

  10. Hiwase DK, White D, Zrim S, Saunders V, Melo JV, Hughes TP . Nilotinib-mediated inhibition of ABCB1 increases intracellular concentration of dasatinib in CML cells: implications for combination TKI therapy. Leukemia 2010; 24: 658–660.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Research grant for this study was supplied by Novartis.

Author information

Authors and Affiliations

  1. Cancer Treatment and Research Center at The University of Texas Health Science Center, Institute for Drug Development, San Antonio, TX, USA

    F J Giles

  2. Department of Hematology, S. Eugenio Hospital, Rome, Italy

    E Abruzzese

  3. Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy

    G Rosti & M Baccarani

  4. Department of Hematology, The Catholic University of Korea, Seoul, Korea

    D-W Kim

  5. Department of Hematopoietic Stem Cell and Leukemia Research, City of Hope, Duarte, CA, USA

    R Bhatia

  6. Department of Hematology, Mont-Godinne University Hospital, Yvoir, Belgium

    A Bosly

  7. Hackensack University Medical Center, John Theurer Cancer Center, Hackensack, NJ, USA

    S Goldberg

  8. Department of Hematology, Singapore General Hospital, Singapore

    G L S Kam

  9. Hematology and Stem Cell Transplantation Section, Vanderbilt University Medical Center, Nashville, TN, USA

    M Jagasia

  10. Department of Hematology and BMT, Silesian Medical University, Katowice, Poland

    W Mendrek

  11. Department of Hematology/Oncology, University Hospital Magdeburg, Magdeburg, Germany

    T Fischer

  12. Department of Hematology, CHRU Lille, Lille, France

    T Facon

  13. Department of Hematology/Oncology, University of Frankfurt, Frankfurt, Germany

    U Dünzinger

  14. Department of Hematology, Imperial College London, Hammersmith Hospital, London, UK

    D Marin

  15. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany

    M C Mueller

  16. Department of Oncology, Novartis, East Hanover, NJ, USA

    Y Shou & N J Gallagher

  17. Department of Hematology, University of Chicago, Chicago, IL, USA

    R A Larson

  18. Institut Bergonié, Université Victor Ségalen Bordeaux, Bordeaux, France

    F-X Mahon

  19. Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J Cortes & H M Kantarjian

Authors
  1. F J Giles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Abruzzese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Rosti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D-W Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R Bhatia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Bosly
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G L S Kam
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Jagasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. W Mendrek
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T Facon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. U Dünzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. D Marin
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M C Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Y Shou
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. N J Gallagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. R A Larson
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. F-X Mahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. M Baccarani
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. J Cortes
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. H M Kantarjian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F J Giles.

Ethics declarations

Competing interests

Francis J Giles, Elisabetta Abruzzese, Gianantonio Rosti, Dong-Wook Kim, Ravi Bhatia, Andre Bosly, Stuart Goldberg, Grace Kam, Madan Jagasia, Wlodzimierz Mendrek, Thomas Fischer, Thierry Facon, Ulrich Dünzinger, David Marin, Martin C Mueller, Richard Larson, Francois-Xavier Mahon, Michele Baccarani, Jorge Cortes and Hagop Kantarjian have received research funding from Novartis Pharmaceuticals. Yaping Shou and Neil Gallagher are employees of Novartis Pharmaceuticals.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giles, F., Abruzzese, E., Rosti, G. et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia 24, 1299–1301 (2010). https://doi.org/10.1038/leu.2010.110

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2010.110

Keywords

This article is cited by

Search

Advanced search

Quick links